The article by Toby Lawrence discusses the role of the nuclear factor NF-κB pathway in inflammation, highlighting its complex and dual nature as both a pro- and anti-inflammatory signaling molecule. NF-κB is primarily activated by proinflammatory cytokines such as IL-1 and TNFα, leading to the expression of proinflammatory genes. However, recent genetic studies in mice have revealed that NF-κB also plays a role in anti-inflammatory processes, such as epithelial cell survival and mucosal barrier integrity. The article explores the two main pathways of NF-κB activation: the canonical pathway, which is triggered by microbial products and proinflammatory cytokines, and the alternative pathway, which is activated by TNF-family cytokines. The canonical pathway is regulated by IKKβ, while the alternative pathway is regulated by IKKα. The article also discusses the specific roles of different NF-κB components, such as RelA and p50, in inflammation and their potential therapeutic implications. Overall, the data suggest that while NF-κB is a key player in inflammation, its role is more nuanced and complex than previously thought, making it a challenging target for anti-inflammatory treatments.The article by Toby Lawrence discusses the role of the nuclear factor NF-κB pathway in inflammation, highlighting its complex and dual nature as both a pro- and anti-inflammatory signaling molecule. NF-κB is primarily activated by proinflammatory cytokines such as IL-1 and TNFα, leading to the expression of proinflammatory genes. However, recent genetic studies in mice have revealed that NF-κB also plays a role in anti-inflammatory processes, such as epithelial cell survival and mucosal barrier integrity. The article explores the two main pathways of NF-κB activation: the canonical pathway, which is triggered by microbial products and proinflammatory cytokines, and the alternative pathway, which is activated by TNF-family cytokines. The canonical pathway is regulated by IKKβ, while the alternative pathway is regulated by IKKα. The article also discusses the specific roles of different NF-κB components, such as RelA and p50, in inflammation and their potential therapeutic implications. Overall, the data suggest that while NF-κB is a key player in inflammation, its role is more nuanced and complex than previously thought, making it a challenging target for anti-inflammatory treatments.